POLYMORPHISM WITHIN T4/LEU3 AND SLE

点击翻译按钮获取中文摘要

The T 4/Leu3 moleculeis a T cell differentiation antigen which has been shown to help in B cell differentiation, to interact with class II major histocompatibility (MHC) antigens on non-T cells, and to form part of the receptor complex for the HTLV-III virus. Although originally believed to be monomorphic, this molecule has recently been shown to manifest a limited polymorphism. It is hypothesized that the cellular function of T cells is dependent on the T4/Leu3 phenotype expressed. Three specific aims will be addressed. 1) Characterization of the polymorphism within T4/Leu3. Monoclonal antibodies (mAb) will be generated from mice by immunizing with T cells from individuals with known differences at the epitope recognized by mAb OKT4 (T4 epitope). It is anticipated that some of these mAb will recognize other polymorphic epitopes and will be used to screen different individuals for expression of the given epitope. 2) Assessment of in vitro function by T cells expressing different T4/Leu3 phenotypes. T cells expressing different T4/Leu3 phenotypes will be tested for help and suppression in B cell differentiation as well as proliferation in response to recall antigens, mitogens, and autologous and allogeneic MHC antigens. Blocking experiments using mAb directed against different epitopes will be performed to test whether different portions of the T4/Leu3 molecule play important roles for different functions. In addition to test the T4/Leu3-class II MHC antigen interactions, the effects of mAb against class II MHC antigens will be assessed and correlated with T4/Leu3 phenotype. 3) Correlation of T4Leu3 phenotype with susceptibility to systemic lupus erythematosus (SLE). Initial studies have suggested an association between T4 epitope deficiency and development of SLE. Normal individuals, SLE patients, and patients with non-rheumatologic disease will be screened for T4/Leu3 phenotype to confirm these initial observations and to correlate T4/Leu3 phenotype with clinical and serologic manifestations.